rs1535775

Positions:

• chr13-37646822-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016179.4(TRPC4):​c.2079+4443T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.73 in 152,164 control chromosomes in the GnomAD database, including 41,404 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.73 (41404 hom., cov: 32)
• Consequence: TRPC4 NM_016179.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.778

Genes affected

TRPC4 (HGNC:12336): (transient receptor potential cation channel subfamily C member 4) This gene encodes a member of the canonical subfamily of transient receptor potential cation channels. The encoded protein forms a non-selective calcium-permeable cation channel that is activated by Gq-coupled receptors and tyrosine kinases, and plays a role in multiple processes including endothelial permeability, vasodilation, neurotransmitter release and cell proliferation. Single nucleotide polymorphisms in this gene may be associated with generalized epilepsy with photosensitivity. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPC4	NM_016179.4	c.2079+4443T>C		intron_variant		ENST00000379705.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPC4	ENST00000379705.8	c.2079+4443T>C		intron_variant		1	NM_016179.4	P4

Frequencies

GnomAD3 genomes AF: 0.731 AC: 111071 AN: 152046 Hom.: 41387 Cov.: 32

Gnomad AFR AF: 0.678

Gnomad AMI AF: 0.867

Gnomad AMR AF: 0.661

Gnomad ASJ AF: 0.840

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.675

Gnomad FIN AF: 0.749

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.804

Gnomad OTH AF: 0.748

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.730 AC: 111136 AN: 152164 Hom.: 41404 Cov.: 32 AF XY: 0.720 AC XY: 53587 AN XY: 74386

Gnomad4 AFR AF: 0.678

Gnomad4 AMR AF: 0.660

Gnomad4 ASJ AF: 0.840

Gnomad4 EAS AF: 0.300

Gnomad4 SAS AF: 0.676

Gnomad4 FIN AF: 0.749

Gnomad4 NFE AF: 0.804

Gnomad4 OTH AF: 0.746

Alfa AF: 0.759 Hom.: 5478

Bravo AF: 0.717

Asia WGS AF: 0.503 AC: 1751 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.15
DANN	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1535775; hg19: chr13-38220959;